Adriamycin, an antibiotic compound which is useful in the treatment of certain tumors is described and claimed in U.S. Pat. No. 3,590,028 to Arcamone et al. A further procedure for the preparation of adriamycin will be found in U.S. Pat. No. 3,803,124 to Arcamone et al which also discloses that adriamycin may be prepared from daunomycin or its aglycone daunomycinone. The coupling of daunomycinone with the appropriate sugar to yield daunomycin (also known as daunorubicin) is found in Acton, et al J.Med.Chem. 17, 659 (1974).
Certain analogs of daunomycin which are disclosed as being useful in the therapy of neoplastic ailments are set forth in Belgian Pat. No. 830,090 to Patelli, et al Societa Farmaceutici Italia, S.p.a. Included among these analogs are 4-demethoxydaunomycin,1-methoxydaunomycin,1,4-and 2,3-dimethyl-4-demethoxydaunomycin.
Methods of synthesizing daunomycinone are disclosed in Kende, et al U.S. Pat. No. 4,070,382 and the analogs thereof in Kende, et al U.S. Pat. No. 4,021,457 which are both incorporated herein by reference.
In both of the above-identified Kende, et al methods the key step in providing the tetracyclic skeleton involves a Diels-Alder reaction between the appropriate quinizarinquinone (I) and an ester of 2-hydroxy-1,3-butadiene most suitably the acetyl ester.
It has been found that the necessary esters of 2-hydroxy-1,3-butadiene are difficult and expensive to prepare and efforts were directed to the provision of an inexpensive, readily available alternative diene which would provide not only the desired tetracyclic skeleton but also a moiety at the 9 position of said skeleton which could be readily converted to the desired 9-keto group.